This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project compares brain and cognitive decline in female Homo sapiens, Pan troglodytes and Macaca mulatta. We have collected behavioral data from 436 healthy human females on tasks derived for nonhuman primates (NHPs). Results confirm that humans show age-related decline on NHP-derived tasks designed to measure visual recognition memory, spatial working memory, motor function, and executive function. Parallel studies on rhesus monkeys (n=24) have confirmed the expected pattern of decline in monkeys. However, results in chimpanzees (n=36) have been surprising in that the chimpanzee appears to be somewhat resistant to age-related changes in some tests. Thus, while all three species show deficits in executive function, as measured by our computerized Conceptual Set Shifting Task, only humans and rhesus monkeys, but not chimpanzees, show a decline in spatial working memory. Another aim of this project is to assess cognitive function in AD and MCI patients, enrolled as subjects in the Emory Alzheimer Disease Research Center (ADRC), which has also made progress. Twenty-six ADRC subjects have been enrolled, and preliminary results confirm that they too show age-related decline in the CSST and DRST tasks. Additional subjects are now being tested. Many theories of aging suggest that the human's aging phenotype, including impairment and the uniquely human susceptibility to Alzheimer Disease, is a result of selection pressure that shaped our species. This unique study of the differences among three primates will help us understand evolutionary and physiological processes that may paradoxically underlie both our uniquely human longevity and our susceptibility to age-related decline.